This invention relates to multiplex assays for simultaneous detection of the presence and optionally semi-quantization of drugs in a sample, for instance a sample of a human or other (non-human) mammalian body fluid, or of the body fluid of a non-mammalian vertebrate. By “drugs” we mean to include narcotics, prescription drugs, over-the-counter medicines, and their metabolites. The invention includes both methods of conducting such assays and kits for use in such methods. As used herein, the term “drug” or “drugs” is meant to include the active substances, derivatives of those substances, for instance salts or esters, and metabolites of either the drugs or their derivatives.
Determination of drugs in a sample of a bodily fluid, particularly a human or mammalian fluid sample, is needed in several different situations. In a law-enforcement environment it may be necessary to ascertain whether a suspect or a victim has taken one or more narcotics or other drugs that may be abused. Similarly in health situations such as hospital emergency rooms and other hospital units or in a drug treatment program it may be necessary to determine whether a patient has taken one or more of such drugs. In both situations the person whose body fluid is being tested may not be in a condition to provide information about drugs that have been taken, or may be lying, or absent, or deceased. If the patient is an animal, again there may be no-one present to provide information about drugs that may have been administered.
In such situations it is common to run a series of discrete tests for individual drugs and/or their metabolites, each test requiring its own set of reagents, controls and calibrators. However, it would be far more convenient, and would consume significantly less time in running the test (and time could be critical in some cases), to have a multiplex assay, in which a number of assays could be run simultaneously, and a single or combined result produced.
Multiplex assays have been developed for a number of applications. A known problem, however, in designing such assays is the potential for what is known as “cross-talk”, i.e. the potential for a particular antibody to bind to a plurality of drug conjugates, especially conjugates containing related drugs such as amphetamine and methamphetamine. Such problem is discussed, for example, in U.S. Pat. No. 5,525,524, whose inventors proposed the solution of including a crosstalk inhibitor in the assay.
Test procedures for simultaneously assaying for the presence of two or more drugs are described in U.S. Pat. Nos. 5,851,776 of Valkirs and 6,777,190 of Buechler et al. These all relate to lateral-flow chromatographic assays on a membrane or other porous or non-porous material. At least two products of this type are currently available commercially: the Triage® drugs-of-abuse panel from Biosite Incorporated (San Diego, Calif., USA) and the TOX-See™ drug screen test from Bio-Rad Laboratories, Inc. (Hercules, Calif., USA). However, these assays are not optimal for larger-scale automated testing and are only qualitative, not semi-quantitative, assays. U.S. published application 2006/99664 of Ullman et al. describes a multiplex assay for detection of drugs, but the example is qualitative and involves only two drugs.